In collaboration with the Division of Cancer Epidemiology and Genetics, National Cancer Institute, we have characterized the role of a POT1 variant in human hematopoietic malignancies. CEG group has conducted the whole exome sequencing of patients from 41 families with Hodgkin lymphoma and identified two families with distinct heterozygous rare coding variants in POT1 (D224N and Y36H), both in a highly conserved region of the gene. We found that (1) the POT1 D224N mutant did not bind to a single-stranded telomere oligonucleotide in vitro suggesting the mutation perturbs POT1s ability to bind to the telomeric G-rich overhang; (2) human HT1080 cells expressing POT1 D224N and lymphoblastoid cells carrying Y36H both showed increased telomere length and fragility in comparison to wild type cells. This strongly suggests that mutant POT1 causes chromosome instability and may play a role in lymphomagenesis in these families. A paper reporting these results was published in Br J Haematol. 181:372-377, 2018.